Folding self-expandable intravascular stent

ABSTRACT

This invention is a medical device and a method of using it. The device is a foldable stent or stent-graft which may be percutaneously deliverable with (or on) an endovascular catheter or via other surgical or other techniques and then expanded. The expandable stent structure utilizes at least one torsional sector which allows it to be folded to a very small diameter prior to deployment as a stent. The stent may be expanded with the use of an installation device such as a balloon but preferably is used as a self-expandable device. The stent may be flared on at least one of its ends to promote smooth blood flow at that flare and to assure that the stent will remain in the chosen position within the body. The stent&#39;s configuration allows it to be folded or otherwise compressed to a very small diameter prior to deployment without changing the length of the stent. The graft component cooperating with the stent is tubular and preferably is a blood-compatible collagenous material which may, if desired, be reinforced with fibers. The tubular member may be cast onto or otherwise attached or imbedded into the stent structure to form a stent-graft.

This application is a continuation of application Ser. No. 08/558,225,filed Nov. 17, 1995, now abandoned which is a continuation ofapplication Ser. No. 08/222,263, filed Apr. 1, 1994, now abandoned.

FIELD OF THE INVENTION

This invention is a medical device and a method of using it. The deviceis a foldable stent or stent-graft which may be percutaneouslydeliverable with (or on) an endovascular catheter or via other surgicalor other techniques and then expanded. The expandable stent structureutilizes at least one torsional sector which allows it to be folded to avery small diameter prior to deployment as a stent. The stent may beexpanded with the use of an installation device such as a balloon butpreferably is used as a self-expandable device. The stent may be flaredon at least one of its ends to promote smooth blood flow at that flareand to assure that the stent will remain in the chosen position withinthe body. The stent's configuration allows it to be folded or otherwisecompressed to a very small diameter prior to deployment without changingthe length of the stent. The graft component cooperating with the stentis tubular and preferably is a blood-compatible collagenous materialwhich may, if desired, be reinforced with fibers. The tubular member maybe cast onto or otherwise attached or imbedded into the stent structureto form a stent-graft.

The stent-graft may be used to reinforce vascular irregularities, toprovide a smooth nonthrombogenic interior vascular surface for diseasedareas in blood vessels, or to increase blood flow past a diseased areaof a vessel by mechanically improving the interior surface of thevessel. The inventive stent-graft is especially suitable for use withinsmaller vessels between 2 mm and 6 mm in diameter but is equallysuitable for significantly larger vessels. The invention provides astent which is self-expanding, kink-resistant, easily bent along itslongitudinal axis, does not change its length during that expansion, andis able to provide collapsible support for otherwise frangible graftmaterial.

The invention involves procedures for deploying stents or stent-graftswhich have been folded, bound, or otherwise collapsed to significantlysmaller diameters for insertion into a human or animal body. When usedwith super-elastic alloys, the stent may be collapsed at a convenienttemperature either above or, preferably, below the transitiontemperature of the alloy. The deployment procedures may involve the useof an outer sleeve to maintain the stent or stent-graft at a reduceddiameter to hold and then to release the device.

BACKGROUND OF THE INVENTION

Treatment or isolation of vascular aneurysms or of vessel walls whichhave been thinned or thickened by disease has traditionally been donevia surgical bypassing with vascular grafts. Shortcomings of thisprocedure include the morbidity and mortality associated with surgery,long recovery times after surgery, and the high incidence of repeatintervention needed due to limitations of the graft or of the procedure.Vessels thickened by disease are currently sometimes treated lessinvasively with intraluminal stents that mechanically hold these vesselsopen either subsequent to or as an adjunct to a balloon angioplastyprocedure. Shortcomings of current stents include the use of highlythrombogenic materials (stainless steels, tantalum, ELGILOY) which areexposed to blood, the general failure of these materials to attract andsupport functional endothelium, the irregular stent/vessel surface thatcauses unnatural blood flow patterns, and the mismatch of compliance andflexibility between the vessel and the stent.

Important to this invention is the use of less invasive intraluminaldelivery and, in a preferred aspect, placement of a nonthrombogenicblood-carrying conduit having a smooth inner lumen which willendothelize. The most preferred biologic material chosen for the innerlayer of the inventive stent-graft is collagen-based and, although itwill fold with ease, is otherwise fairly frangible or inelastic in thatit has very little ability to stretch. Mounting a collagen tube on theoutside of or as a part of a balloon-expandable stent will usually causethe tube to tear. Mounting such a collagen tube on the inside of aballoon expandable stent will yield a torn irregular surface exposed toblood flow. Further, balloon expandable devices that rely upon plasticdeformation of the stent to achieve a deployed shape are subject toabrupt closure as a result of trauma when the devices are placed in avessel near the skin surface or across a joint or ligament. Thoseself-expanding stents which rely on the shortening of the stent uponradial expansion at deployment may cause vessel tearing problems similarto those observed with the use of balloon expandable devices. Obviously,stents which shorten during deployment are also subject to deploymentplacement inaccuracies.

The most desired variations of this invention involve a stent-graftwhich is self-expanding, which does not shorten upon delivery, which hasexcellent longitudinal flexibility, which has high radial compliance tothe vessel lumen, exposes the blood to a smooth, nonthrombogenic surfacecapable of supporting endothelium growth.

The inventive device may be delivered in a reduced diameter and expandedto maintain the patency of any conduit or lumen in the body. An area inwhich the inventive stent and stent graft is particularly beneficial isin the scaffolding of atherosclerotic lesions in the cardiovascularsystem to establish vessel patency, prevention of thrombosis, and thefurther prevention of restenosis after angioplasty. In contrast to manyof the stents discussed below having metallic struts intruding into theblood flow in the vessel lumen which generate turbulence and createblood stasis points initiating thrombus formation, the smooth,continuous surface provided by the preferred tubular collagen-basedinner conduit of our invention provides a hemodynamically superiorsurface for blood flow.

The non-thrombogenic properties of the most preferred sPEG collagensurface results in a less thrombogenic device. Clinically, this allows amore moderate anti-coagulation regimen to be used. As a result, the rateof bleeding complications, a major drawback associated with stenting,may be reduced. The absence of gaps or holes in the graft structurebetween stent struts of our invention allows the tacking of both largeand small flaps and tears in the vessel wall. These flaps disrupt bloodflow and attract thrombus. The disruption of the natural anti-thromboticcovering of endothelium only worsens the condition. The collagen-basedbarrier we interpose between blood and a disrupted or injured portion ofthe vessel wall serves to mask injured intimal or medial layers fromblood, thereby preventing thrombus formation and intimal proliferationwhich may lead to restenosis.

The presence of our inventive stent-graft acts as a mechanical barrierpreventing tissue from proliferating into or impinging the lumen. Thenature of the bioactivity of the collagen and the smoother flowcharacteristics at the blood-contacting surface are conducive toendothelial cell attachment and growth thereby assuring the long-termblood compatibility of the device.

Mechanically, our inventive helical stent structure provides a goodcombination of radial strength and flexibility. The structure is alsoradially resilient. It can be completely crushed or flattened and yetspring open again once the obstructive loading is removed. This abilityis important for use in exposed portions of the body around theperipheral vasculature or around joints. The stent-graft can sustain acrushing traumatic blow or compression from the bending of a joint andstill return to the open configuration once the load is removed.

With regard to delivery, the self-expansion mechanism eliminates theneed for a balloon catheter and the associated balloon rupture problemsoften associated with balloons. In addition, the absence of the bulk ofa balloon in the delivery mechanism allows a smaller delivery profile tobe achieved. Unlike some other self-expanding stent designs, thisstent-graft maintains a constant length throughout the expansionprocess. Thus, the stent-graft would not have some of the positioningproblems associated with many other self-expanding stents. In treatinglonger lesions, our self-expanding design eliminates the need forspecial long balloons or repositioning of the balloon between inflationsin order to expand the entire length of the stent.

When used as a conventional vascular graft or intraluminal graft, ourmost preferred stent-grafts offer a number of advantages over existingtechnologies. Unlike expanded polytetrafluoroethylene (PTFE) grafts, thecollagen-based material supports endothelial cell growth and isincorporated into the surrounding tissue. As an intraluminal graft, thedevice has several advantages. The wall thickness may be made thinnerthan either of current stents and expanded PTFE or of tanned, reinforcedbiologic grafts. When placed inside the lumen of a vessel, a thin-walledgraft results in a larger opening for blood flow resulting in improvedhemodynamics. Lastly, when used as an intraluminal graft, there is noanastomosis site. Anastomosis sites are thought to be a common source ofproblems associated with graft failures.

The impermeability of the preferred stent-graft makes it suitable forshunting and thereby hydraulically isolating aneurysms. The expansileproperties derived from the stent structure provide a secure anchor tothe vessel wall. The stent reinforces the collagen-based tubularcomponent, much as a fiber tube would, increasing the burst strength ofthe stent-graft.

Therapeutic compounds may be linked, conjugated, or otherwise moreeasily bound to the organic graft material (or to its substituents, suchas PEG) than to the surface of a metallic structure. Localized drugdelivery is desirable in preventing thrombosis or restenosis.Therapeutically effective doses may be administered to the target areawithout systemic concentrations being raised. This capability is ofgreat benefit in reducing side-effects and complications associated withdrug therapy.

Therapeutic agents may be delivered out of the collagen matrix bydiffusion. Alternatively, these agents may be bound temporarily orpermanently on the collagen surfaces. Different agents may be bound onthe inner and outer surfaces to achieve different therapeutic ends. Forexample, a drug to minimize thrombus formation might be appropriate forthe inside, blood-contacting surface, while a drug which would inhibitsmooth muscle cell proliferation might be appropriate on the outersurface. Drugs can be chemically or physically bound to either the sPEGor the collagen molecules.

Stents

There are a variety of different shapes disclosed in the prior art forendovascular stents.

Wallsten, U.S. Pat. No. 4,655,771, suggests a vascular prosthesis fortransluminal implantation which is made up of a flexible tubular bodyhaving a diameter that is varied by adjusting the axial separation ofthe two ends of the body relative to each other. In general, the bodyappears to be a woven device produced of various plastics or stainlesssteel.

U.S. Pat. No. 4,760,849, to Kroph, shows the use of a ladder-shaped coilspring which additionally may be used as a filter in certain situations.

Porter, U.S. Pat. No. 5,064,435, suggests a stent made up of two or moretubular stent segments which may be deployed together so to produce asingle axial length by a provision of overlapping areas. This concept isto permit the use of segments of known length, which, when deployed, maybe used together in overlapping fashion additively to provide a stent ofsignificant length.

Quan-Gett, U.S. Pat. No. 5,151,105, discloses an implantable,collapsible tubular sleeve apparently of an outer band and an innerspring used to maintain the sleeve in a deployed condition.

Wall, U.S. Pat. No. 5,192,307, suggests a stent having a number of holestherein and which is expandable using an angioplasty balloon so to allowratchet devices or ledges to hold the stent in an open position once itis deployed.

Perhaps of more relevance are the patents using wire as the stentmaterial.

Gianturco, U.S. Pat. No. 4,580,568, in U.S. Pat. Nos. 4,580,568 and5,035,706 describe stents formed of stainless steel wire arranged in aclosed zigzag pattern. The stents are compressible to a reduced diameterfor insertion into and removal from a body passageway. The stents appearto be introduced into the selected sites by discharge of the collapsedzigzag wire configuration from the tip of a catheter.

Wallsten, U.S. Pat. No. 4,655,771, suggests a prosthesis fortransluminal implantation which is made up of a flexible tubular bodyhaving a diameter that is varied by adjusting the axial displacement ofthe two ends of the body relative to each. In general, the body appearsto be a woven device produced of various plastics or stainless steel.

U.S. Pat. No. 4,760,849, to Kroph, shows the use of a ladder-shaped coilspring which additionally may be used as a filter in certain situations.

U.S. Pat. Nos. 4,830,003 and 5,104,404, to Wolff et al., shows a stentof a zigzag wire configuration very similar in overall impression to theGianturco device. However, the stent is said to be self-expanding andtherefore does not need the angioplasty balloon for its expansion.

Hillstead, U.S. Pat. No. 4,856,516, suggests a stent for reinforcingvessel walls made from a single elongated wire. The stent produced iscylindrical and is made up of a series of rings which are, in turn,linked together by half-hitch junctions produced from the singleelongated wire.

Wiktor, U.S. Pat. Nos. 4,649,992, 4,886,062, 4,969,458, and 5,133,732,shows wire stent designs using variously a zigzag design or, in the caseof Wiktor '458, a helix which winds back upon itself. Wiktor '062suggests use of a wire component made of a low-memory metal such ascopper, titanium or gold. These stents are to be implanted using aballoon and expanded radially for plastic deformation of the metal.

Wiktor '458 is similarly made of low-memory alloy and is to beplastically deformed upon its expansion on an angioplasty balloon.

Wiktor '732 teaches the use of a longitudinal wire welded to each turnof the helically wound zig-zag wire which is said to prevent thelongitudinal expansion of the stent during deployment. A furthervariation of the described stent includes a hook in each turn of thehelix which loops over a turn in an adjacent turn. Neither variationincludes a flexible linkage between adjacent helices.

MacGregor, U.S. Pat. No. 5,015,253, shows a tubular non-woven stent madeup of a pair of helical members which appear to be wound using opposite"handedness". The stent helices desirably are joined or secured at thevarious points where they cross.

Porter, U.S. Pat. No. 5,064,435, suggests a stent made up of two or moretubular stent segments which may be deployed together so to maintain asingle axial length by a provision of overlapping areas. This concept isto permit the use of segments of known length, which, when deployed, maybe used together in overlapping fashion to additively provide a stent ofsignificant length.

Pinchuk, in U.S. Pat. Nos. 5,019,090, 5,092,877, and 5,163,958, suggestsa spring stent which appears to circumferentially and helically windabout as it is finally deployed except, perhaps, at the very end link ofthe stent. The Pinchuk '958 patent further suggests the use of apyrolytic carbon layer on the surface of the stent to present a poroussurface of improved antithrombogenic properties. The helices are notlinked to each other, however, nor is there any suggestion that thehelices be maintained in a specific relationship either as deployed oras kept in the catheter prior to deployment.

U.S. Pat. No. 5,123,917, to Lee, suggests an expandable vascular grafthaving a flexible cylindrical inner tubing and a number of "scaffoldmembers" which are expandable, ring-like, and provide circumferentialrigidity to the graft. The scaffold members are deployed by deformingthem beyond their plastic limit using, e.g., an angioplasty balloon.

Tower, in U.S. Pat. Nos. 5,161,547 and 5,217,483, shows a stent formedfrom a zig-zag wire wound around a mandrel in a cylindrical fashion. Itis said to be made from "a soft platinum wire which has been fullyannealed to remove as much spring memory as possible." A longitudinalwire is welded along the helically wound sections much in the same wayas was the device of Wiktor.

There are a variety of disclosures in which super-elastic alloys such asnitinol are used in stents. See, U.S. Pat. No. 4,503,569, to Dotter;U.S. Pat. No. 4,512,338, to Balko et al.; U.S. Pat. No. 4,990,155, toWilkoff; U.S. Pat. No. 5,037,427, to Harada, et al.; U.S. Pat. No.5,147,370, to MacNamara et al.; U.S. Pat. No. 5,211,658, to Clouse; andU.S. Pat. No. 5,221,261, to Termin et al. None of these referencessuggest a device having discrete, individual, energy-storing torsionalmembers as are required by this invention.

Jervis, in U.S. Pat. Nos. 4,665,906 and 5,067,957, describes the use ofshape memory alloys having stress-induced martensite properties inmedical devices which are implantable or, at least, introduced into thehuman body.

Cragg (European Patent Application 0,556,850) discloses an intraluminalstent made up of a continuous helix of zig-zag wire and having loops ateach apex of the zig-zags. Those loops on the adjacent apexes areindividually tied together to form diamond-shaped openings among thewires. The stent may be made of a metal such as nitinol (col. 3, lines15-25 and col. 4, lines 42+) and may be associated with a"polytetrafluoroethylene (PTFE), dacron, or any other suitablebiocompatible material". Those biocompatible materials may be inside thestent (col. 3, lines 52+) or outside the stent (col. 4, lines 6+). Thereis no suggestion that the zig-zag wire helix be re-aligned to be "inphase" rather than tied in an apex-to-apex alignment. The alignment ofthe wire and the way in which it is tied mandates that it expand inlength as it is expanded from its compressed form.

Grafts

As was noted above, the use of grafts in alleviating a variety ofvascular conditions is well known. Included in such known graftingdesigns and procedures are the following.

Medell, U.S. Pat. No. 3,479,670, discloses a tubular prothesis adaptedto be placed permanently in the human body. It is made of framework orsupport of a synthetic fiber such as DACRON or TEFLON. The tube is saidto be made more resistant to collapse by fusing a helix of apolypropylene monofilament to its exterior. The reinforced fabric tubeis then coated with a layer of collagen or gelatin to render the tubing(to be used as an esophageal graft) impermeable to bacteria or fluids.

Sparks, in U.S. Pat. Nos. 3,514,791, 3,625,198, 3,710,777, 3,866,247,and 3,866,609, teach procedures for the production of various graftstructures using dies of suitable shape and a cloth reinforcing materialwithin the die. The die and reinforcement are used to grow a graftstructure using a patient's own tissues. The die is implanted within thehuman body for a period of time to allow the graft to be produced. Thegraft is in harvested and implanted in another site in the patient'sbody by a second surgical procedure.

Braun, in U.S. Pat. No. 3,562,820, shows a biological prosthesismanufactured by applying onto a support of a biological tissue (such asserosa taken from cattle intestine) a collagen fiber paste. Theprocedure is repeated using multiple layers of biological tissue andcollagen fiber paste until a multi-layer structure of the desired wallthicknesses is produced. The prosthesis is then dried and removed priorto use.

Dardik et al, U.S. Pat. No. 3,974,526, shows a procedure for producingtubular prostheses for use in vascular reconstructive surgeries. Theprosthesis is made from the umbilical cord of a newly born infant. It iswashed with a solution of 1 percent hydrogen peroxide and rinsed withRinger's lactate solution. It is then immersed in a hyaluronidasesolution to dissolve the hyaluronic acid coating found in the umbilicalcord. The vessels are then separated from the cord and their naturalinterior valving removed by use of a tapered mandrel. The vessels arethen tanned with glutaraldehyde. A polyester mesh support is applied tothe graft for added support and strength.

Whalen, U.S. Pat. No. 4,130,904, shows a prosthetic blood conduit havingtwo concentrically associated tubes with a helical spring between them.Curved sections in the tube walls help prevent kinking of the tube.

Ketharanathan, U.S. Pat. No. 4,319,363, shows a procedure for producinga vascular prosthesis suitable for use as a surgical graft. Theprosthesis is produced by implanting a rod or tube in a living host andallowing collagenous tissue to grow on the rod or tube in the form ofcoherent tubular wall. The collagenous implant is removed from the rodor tube and tanned in glutaraldehyde. The prosthesis is then ready foruse.

Bell, U.S. Pat. No. 4,546,500, teaches a method for making a vesselprosthesis by incorporating a contractile agent such as smooth musclecells or platelets into a collagen lattice and contracting the latticearound a inner core. After the structure has set, additional layers areapplied in a similar fashion. A plastic mesh sleeve is desirablysandwiched between the layers or imbedded within the structure toprovide some measure of elasticity.

Hoffman Jr. et al, U.S. Pat. No. 4,842,575, shows a collagen impregnatedsynthetic vascular graft. It is made of a synthetic graft substrate anda crosslinked collagen fibril. It is formed by depositing a aqueousslurry of collagen fibrils into the lumen of the graft and massaging theslurry into the pore structure of the substrate to assure intimateadmixture in the interior. Repeated applications and massaging anddrying is said further to reduce the porosity of the graft.

Alonoso, U.S. Pat. No. 5,037,377, is similar in overall content to theHoffman Jr. et al patent discussed above except that, in addition tocollagen fibers, soluble collagen is introduced into the fabric. Asuitable cross-linking agent such as glutaraldehyde is used to bondadjacent collagen fibers to each other.

Slepian et al, U.S. Pat. No. 5,213,580, teaches a process described as"paving" or "stabilizing by sealing the interior surface of a bodyvessel or organ" by applying a biodegradable polymer such as apolycaprolactone. The polymer is made into a tubular substrate, placedin position, and patched into place.

Stent-Grafts

A variety of stent-graft designs are shown in the following literature.

Perhaps the most widely known such device is shown in Ersek, U.S. Pat.No. 3,657,744. Ersek shows a system for deploying expandable,plastically deformable stents of metal mesh having an attached graftthrough the use of an expansion tool.

Palmaz describes a variety of expandable intraluminal vascular grafts ina sequence of patents: U.S. Pat. Nos. 4,733,665; 4,739,762; 4,776,337;and 5,102,417. The Palmaz '665 patent suggests grafts (which alsofunction as stents) that are expanded using angioplasty balloons. Thegrafts are variously a wire mesh tube or of a plurality of thin barsfixedly secured to each other. The devices are installed, e.g., using anangioplasty balloon and consequently are not seen to be self-expanding.

The Palmaz '762 and '337 patents appear to suggest the use ofthin-walled, biologically inert materials on the outer periphery of theearlier-described stents.

Finally, the Palmaz '417 patent describes the use of multiple stentsections each flexibly connected to its neighbor.

Rhodes, U.S. Pat. No. 5,122,154, shows an expandable stent-graft made tobe expanded using a balloon catheter. The stent is a sequence ofring-like members formed of links spaced apart along the graft. Thegraft is a sleeve of a material such as expanded a polyfluorocarbon,e.g., GORETEX or IMPRAGRAFT.

U.S. Pat. No. 5,195,984, to Schatz, shows an expandable intraluminalstent and graft which is related to the Palmaz patents discussed above.The patent discusses in addition the use of flexibly-connecting,adjacent vascular grafts so to allow flexibility of the overallstructure in curving body lumen.

Finally, there are known vascular grafts using collagenous tissue withreinforcing structure. For instance, Pinchuk, in U.S. Pat. Nos.4,629,458 and 4,798,606, suggests the use of collagen with some othertype of fibrous structure supporting the collagen as a biograft.Similarly, Sinofsky et al. suggests a partially-cured, collagen-basedmaterial used to form a graft within a blood vessel.

U.S. Pat. No. 5,123,927, to Lee, suggests an expandable vascular grafthaving a flexible cylindrical inner tubing and a number of "scaffoldmembers" which are expandable, ring-like, and provide circumferentialrigidity to the graft. The scaffold members are deployed by deformingthem beyond their plastic limit using, e.g., an angioplasty balloon.

Quan-Gett, U.S. Pat. No. 5,151,105, discloses an implantable,collapsible tubular sleeve apparently of an outer band and an innerspring used to maintain the sleeve in a deployed condition.

We have found that elasticity, or the ability of a material to return toits original shape after a deformation, can be maintained in smallerstents by the distribution of folding deformation throughout thestructure. By incorporating hinge regions into the structure,deformation may be widely dispensed. The hinges include torsion membersoriented parallel to the longitudinal axis of the stent-graft butgenerally perpendicular to the rings. The hinges are positioned at leastat each of the fold points around the circumference where folding isdesired. The circumferentially oriented segments of the stents, whichconnect the torsion bars, pivot about the torsion bars, causing thetorsion members to undergo a twisting deformation. In order to avoidexceeding the elastic limit of the material the length of the torsionmembers may be increased to lower the twist per length or lower thestrain imposed. The orientation of the torsion members is such thattheir length does not increase the circumference of the ring. None ofthe cited references suggest such a device.

SUMMARY OF THE INVENTION

This invention is a medical device and a method of using it. The deviceis a foldable stent or stent-graft which is percutaneously deliverablethrough or over an endovascular catheter or using surgical or othertechniques. The expandable stent structure utilizes torsional sectorswhich allow it to be folded to a very small diameter prior todeployment. The stent may be expanded with the use of an installationdevice such as a balloon but preferably is used as a self-expandabledevice. The graft component is tubular and preferably is a collagenousmaterial which may, if desired, be reinforced with random or wovenfibers. The tubular member preferably is cast onto or otherwise attachedor imbedded into the stent structure. The graft component used tocomplement the stent is tubular and preferably is of a collagenousmaterial which may, if desired, be reinforced with fibers of random,woven, roving, or wound configurations. The tubular member preferably iscast onto or otherwise attached or imbedded into the stent structure.The stent-graft may be used to reinforce vascular irregularities andprovide a smooth interior vascular surface, particularly within smallervessels.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a plan view of an unrolled generic stent form making up theinvention.

FIG. 1B is a quarter view of a generic stent making up the invention.

FIG. 2 is an end view and shows the placement of the inventive stent thebending of certain portions after placement.

FIG. 3 is a cutaway close-up of the inventive stent shown in FIG. 2.

FIG. 4 is an abstracted portion of an inventive stent and shows theconcept of torsion on a portion of the stent.

FIG. 5A shows a stent made according to the invention with insert FIG.5B isolating a torsion member.

FIG. 5C shows the stent of FIG. 5A in a partially folded condition withinsert FIG. 5D isolating a torsion member.

FIG. 5E shows the stent of FIG. 5A in a fully folded condition withinsert FIG. 5F isolating a torsion member.

FIG. 6 shows a plan view of an unrolled stent produced from wire.

FIG. 7A shows a plan view of an unrolled isolated ring making up a stentaccording to the invention.

FIG. 7B shows a quarter view of the rolled isolated ring of FIG. 7A.

FIG. 7C shows a plan view of multiple unrolled isolated rings suitablefor making up a stent according to the invention.

FIGS. 8, 9, and 10 show plan views of variations of unrolled stents madeaccording to the invention.

FIGS. 11A and 11B show end view cutaways of stent-graphs made accordingto the invention.

FIGS. 12A, 12C, and 12E show procedures for folding the stent-graftsmade according to the invention. FIGS. 12B, 12E, and 12F show thecorresponding folded stent-grafts.

FIGS. 13A-13C show a schematic procedure for deploying the inventivestent-grafts.

FIGS. 14A and 15A show front quarter views of folded stents orstent-grafts held in that folded position by a tether wire. FIGS. 14B,14C, 15B, and 15C show end views of the folded stent and of the openstent shown respectively in FIGS. 14A and 15A.

FIGS. 16A-16C show a schematic procedure for deploying the inventivestent-grafts (as shown in FIGS. 14A-14C and 15A-15C) using a tetherwire.

DESCRIPTION OF THE INVENTION

As was noted above, this invention is variously an expandable stent, astent-graft, and a fiber reinforced stent-graft. The stent-graft may bea combination of several components: a thin-walled tube generallycoaxial with the stent, the expandable stent-ring structure, and anoptional network of reinforcing fibers used to reinforce the tubularcomponent. The stent and reinforcing fibers are desirably imbedded inthe wall of the thin-walled tube. The rings are oriented coaxially withthe tube and spaced along its length. The fibers may be formed into anetwork, e.g., a tubular mesh, and typically will extend the entirelength of the tube. The stent-graft may be delivered percutaneouslythrough the vasculature after having been folded to a reduced diameter.Once reaching the intended delivery site, it is expanded to form alining on the vessel wall.

Methods of delivering the various devices through a percutaneouscatheter either with or without expansion aids also form an aspect ofthe invention.

Stent Component

The materials typically used for vascular grafts, e.g., collagen,usually do not have the stiffness or strength by themselves to stay openagainst the radially inward loads found in those vessels and to preventtheir slippage from the chosen deployment site. In order to provide thestrength required, a radially rigid stent structure may be incorporatedinto the stent-graft. Such structures may be constructed of a network ofradially rigid rings. These rings may be oriented coaxially with thetubular component and be spaced apart at intervals along the length ofthe stent-graft in order to preserve its flexibility. The ring (or ringassembly) may or may not be connected together in a single structuralunit. The rings may be placed on the outer or inner surface of thetubular member although it is preferable that the rings be imbedded in acollagen-based tubing wall for ease of integration with the tubing andto prevent exposure of the stent to blood. It is desired that the stentstructure have the strength and flexibility to tack the collagen tubingfirmly and conformally against the vessel wall. In order to minimize thewall thickness of the stent-graft, the stent material should have a highstrength-to-volume ratio. Use of designs according to this inventionprovides stents which are shorter in length than those often used in theprior art. Additionally, the designs do not suffer from a tendency totwist (or helically unwind) or to shorten as the stent is deployed. Aswill be discussed below, materials meeting these criteria includevarious metals and some polymers.

A percutaneously delivered stent-graft must expand from a reduceddiameter, necessary for delivery, to a larger deployed diameter. Thediameters of these devices obviously vary with the size of the bodylumen into which they are placed. The stents of this invention may rangein size from 2.0 mm in diameter (for neurological applications) to 30 mmin diameter (for placement in the aorta). A range of about 2.0 mm to 6.5mm (perhaps to 10 mm) is believed to be desirable. Typically, expansionratios of 2:1 or more are required. These stents are capable ofexpansion ratios of up to 5:1 for the larger stents. Typical expansionratios for use with the stents and stent-grafts of the inventiontypically are in the range of about 2:1 to about 4:1 although theinvention is not so limited. The thickness of the stent materialsobviously varies with the size (or diameter) of the stent and theultimate required yield strength of the folded stent. These values arefurther dependent upon the selected materials of construction. For mostof the stronger alloys, e.g., nitinol and stronger spring stainlesssteels, thicknesses of about 0.002 inches to 0.005 inches is sufficient.For the larger stents, the appropriate thickness for the stent flatstock may be somewhat thicker, e.g., 0.005 to 0.020 inches.

The stent-graft is fabricated in the expanded configuration. In order toreduce its diameter for delivery the stent-graft would be folded alongits length, similar to the way in which a PTCA balloon would be folded.It is desirable, when using super-elastic alloys which are also havetemperature-memory characteristics, to reduce the diameter of the stentat a temperature below the transition-temperature of the alloys. Oftenthe phase of the alloy at the lower temperature is somewhat moreworkable and easily formed. The temperature of deployment is desirablyabove the transition temperature to allow use of the super-elasticproperties of the alloy.

As a generic explanation of the mechanical theory of the inventivestent, reference is made to FIGS. 1A to 4. FIG. 1A is a conceptualschematic of an isolated ring section of the inventive stent device andis intended only to identify and to provide conventions for naming thecomponents of the ring. FIG. 1A shows, in plan view, of the layout ofthe various components of a ring as if they were either to be cut from aflat sheet and later rolled into tubular formation for use as a stentwith welding or other suitable joining procedures taking place at theseam or (if constructed from tubing) the layout as if the tubing was cutopen. The portion of the stent between tie members (100) is designatedas a ring (102) or ring section. Tie members (100) serve to link onering (102) to an adjacent ring (102). A torsion pair (104) is made up ofa cap member (106) and two adjacent torsion members (108). Typically,then, each torsion member (108) will be a component to each of itsadjacent torsion pairs (104).

As ultimately deployed, a roll of the sheet found in FIG. 1A would beentered into the body lumen. Typically, it would be folded in somefashion which will be discussed below. A front quarter perspective viewof the rolled stent is shown in the FIG. 1B. FIG. 2 shows an end view ofthe deployed device. In FIG. 2, the wall of the body vessel (110) isshown with the end view of cap members (106). As is more clearly shownin FIG. 3, the end of the cap members (106) are separated into threedistinct areas: Two opposing sectors (112) and a center sector (114).This distinction is made because as a bending moment is applied alongthe end of that cap member (106), the majority of the flexing in thatcap member takes place along center sector (114). The angle (α) betweenthe opposing sectors (112) is a measure of that flexing.

Further to the understanding of the concept of the stent device is FIG.4. FIG. 4 shows an abstracted section of the sheet found in FIG. 4 inwhich two cap members (106) and a torsion member (108) are shown inisolation from the FIG. 1A sheet. FIG. 4 shows the concept of thetorsional twist angle (τ). For the purposes of discussion here, theangles (α) and (τ) are measured from the same reference, the ends of thecap members (106) and assumes that the two cap members (106) shown inFIG. 4 each define a plane as they are flexed and the two planes sodefined are parallel to each other.

As noted elsewhere, the concept of one very desirable variation of theinvention is that the inventive step, as deployed in FIGS. 2 and 3, isfolded longitudinally and is delivered through the lumen of the catheterin such a way that it is self-restoring once it has been introduced tothe selected body lumen site. This stated desire is not to rule out theuse of the inventive stent or stent-graft with a balloon or expander orother shape-restoring tool if so desired, but the design of the stent ismeant to eliminate the need for (or, at least to minimize the need for)such expanding tools.

With that preliminary background in place, it should be apparent that asimple band of metal will undergo plastic deformation when sufficientforce is applied radially to the outside of the band. The amount offorce needed to cause that plastic deformation will depend on a widevariety of factors, e.g., the type of metal utilized in the band, thewidth of the band, the circumference of the band, the thickness of thematerial making up the band, etc. The act of attempting to fold a bandin such a way to allow it to pass through a lumen having the same orsmaller diameter and yet maintain the axis of the folded ring parallelto the axis of the lumen invites plastic deformation in and of the ring.

The inventive stent uses concepts which can be thought of asdistributing the force necessary to fold the tubular stent into aconfiguration which will fit through a diameter smaller than its relaxedoutside diameter without inducing plastic deformation of the constituentmetal. The force is distributed into two components: a bending componentin cap member (106)--especially in center sector (114)--and a twistingor torsional component in torsion members (108).

Once the concept of distributing the folding or compressing stressesboth into a bending component (as typified by angle α in FIG. 3) and toa twisting component (as typified by angle τ in FIG. 4), and determiningthe overall size of a desired stent, determination of the optimummaterials as well as the sizes of the various integral components makingup the stent becomes somewhat straightforward. Specifically, the length,width, and thickness of torsion members (108), the dimensions of an endcap center sector (114), the thickness of the material, and theremainder may then be determined. Obviously critical to the invention isthe selection of the length, width, and thickness of torsion members(108) and the dimensions of end cap center sector (114) so that thebending angle α and twisting angle τ do not exceed the plasticdeformation value of the selected stent material.

FIGS. 5A, 5B, 5C, 5D, 5E and 5F show, in isolation, the way in which asingle torsion member (108) twists during the step of folding a stentmade according to this invention. FIG. 1A shows a stent substantiallythe same as that shown in FIG. 1B. However, insert FIG. 5B depicts anisolation of torsion member (108). The cap members (106) may also beseen in the inset FIG. 5B. In FIG. 5A, torsion member (108) is nottwisted. That is to say that the angle as shown both in FIG. 5A and inFIG. 4, τ equals zero. In FIG. 5C, the stent (101) has been partiallyfolded along its longitudinal axis generally in the fashion shown in thedrawings described below. In this instance, the twist of torsion member(108) has risen to some value τ="b". This torsional twist stores aportion of the energy required to fold the stent for later use when thestent is released and allowed to self-expand to the condition shown inFIG. 5A. Finally, FIG. 5E shows the stent fully folded along itslongitudinal axis. The stent (101) elides as a single fold in thisinstance. The numbers of folds will be discussed in more detail below.In FIG. 5F, the twist value τ has reached a final value of "c". Theconcept of torsional twist angle was, of course, discussed inconjunction with FIG. 4 above. When the stent is allowed to relax intothe form shown in FIG. 5A, the reverse of these steps is obviouslytaken.

It should be clear that a variety of materials variously metallic, superelastic alloys, and preferably nitinol, are suitable for use in thesestents. Primary requirements of the materials are that they be suitablyspringy even when fashioned into very thin sheets. Various stainlesssteels which have been physically, chemically, and otherwise treated toproduce high springiness are suitable as are other metal alloys such ascobalt chrome alloys (e.g., ELGILOY), platinum/tungsten alloys, andespecially the nickel-titanium alloys generically known as "nitinol".

Nitinol is especially preferred because of its "super-elastic" or"pseudo-elastic" shape recovery properties, i.e., the ability towithstand a significant amount of bending and flexing and yet return toits original form without deformation. These metals are characterized bytheir ability to be transformed from an austenitic crystal structure toa stress-induced martensitic structure at certain temperatures, and toreturn elastically to the austenitic shape when the stress is released.These alternating crystalline structures provide the alloy with itssuper-elastic properties. These alloys are well known but are describedin U.S. Pat. Nos. 3,174,851, 3,351,463, and 3,753,700. Typically,nitinol will be nominally 50.6% (±0.2%) Ni with the remainder Ti.Commercially available nitinol materials usually will be sequentiallymixed, cast, formed, and separately cold-worked to 30-40%, annealed, andstretched. Nominal ultimate yield strength values for commercial nitinolare in the range of 30 psi and for Young's modulus are about 700 kBar.

The '700 patent describes an alloy containing a higher iron content andconsequently has a higher modulus than the Ni-Ti alloys. Nitinol isfurther suitable because it has a relatively high strength to volumeratio. This allows the torsion members to be shorter than for lesselastic metals. The flexibility of the stent-graft is largely dictatedby the length of the torsion member components in the stent structuralcomponent. The shorter the pitch of the device, the more flexible thestent-graft structure can be made. Materials other than nitinol aresuitable. Spring tempered stainless steels and cobalt-chromium alloyssuch as ELGILOY are also suitable as are a wide variety of other known"super-elastic" alloys.

Although nitinol is preferred in this service because of its physicalproperties and its significant history in implantable medical devices,we also consider it also to be suitable for use as a stent because ofits overall suitability with magnetic resonance imaging (MRI)technology. Many other alloys, particularly those based on iron, are ananathema to the practice of MRI causing exceptionally poor images in theregion of the alloy implant. Nitinol does not cause such problems.

Other materials suitable as the stent include certain polymericmaterials, particularly engineering plastics such as thermotropic liquidcrystal polymers ("LCP's"). These polymers are high molecular weightmaterials which can exist in a so-called "liquid crystalline state"where the material has some of the properties of a liquid (in that itcan flow) but retains the long range molecular order of a crystal. Theterm "thermotropic" refers to the class of LCP's which are formed bytemperature adjustment. LCP's may be prepared from monomers such asp,p'-dihydroxy-polynuclear-aromatics or dicarboxy-polynuclear-aromatics.The LCP's are easily formed and retain the necessary interpolymerattraction at room temperature to act as high strength plastic artifactsas are needed as a foldable stent. They are particularly suitable whenaugmented or filled with fibers such as those of the metals or alloysdiscussed below. It is to be noted that the fibers need not be linearbut may have some preforming such as corrugations which add to thephysical torsion enhancing abilities of the composite.

The stent structure may also be made by forming nitinol wire into thedesired configuration. Various segments may be joined by welding. Thedesired structural pattern may be machined out of a flat sheet ofnitinol. The sheet may then be rolled and the opposing edges welded toform a tube. The stent may be machined from nitinol tubing. Carefulcontrol of temperature during the machining step may be had by EDM(electro-discharge-machining), laser cutting, or high pressure watercutting.

FIG. 6 shows a plan view of a variation of the inventive stent (116) inwhich wire forms the various sectors of the stent. Torsion members (118)and end caps (120) forming ring portion (122) is also shown. Wire usedin these variations are typically of stronger alloys, e.g., nitinol andstronger spring stainless steels, and have diameters of about 0.002inches to 0.005 inches. For the larger stents, the appropriate diameterfor the stent wire may be somewhat larger, e.g., 0.005 to 0.020 inches.Adjacent ring portions (122) may be joined by tie members (124). Tiemembers (124) may be welded to the end caps (120) by, e.g., welding. Itshould be apparent that any of the designs shown for cut sheet may, asan alternative, be constructed from wire instead.

FIG. 7A shows a plan view of a ring section (104) of one variation ofthe inventive stent produced from a sheet. In this instance the end caps(106) and torsion members (108) form a single ring section which may berolled and welded into an isolated ring (126) such as shown in FIG. 7B.Because the material chosen for the stent shown in FIGS. 7A and 7B is ahighly elastic material such as nitinol, the length (128) of the torsionsection (108) need not be so long as the length (130) of the end caps(106). FIG. 7C shows a collection of individual rings (126) of the typeshown in FIGS. 6A and 7B as they would be positioned in a stent-graftbut prior to the time they are welded end-to-end.

FIG. 8 shows a variation of the stent having a ring section (132)similar in configuration to that shown in FIGS. 7A, 7B, and 7C butjoined by tie members (134). Those tie members (134) extend from theinside of a torsion pair (138) to the outside of a torsion pair (140) inthe adjacent ring section. The tie members (134) experience no twistingbecause of their placement in the middle of end cap (142). The tiemembers may be offset on the end cap, if so desired, to allow the tiemembers to accept some of the twisting duty.

FIG. 9 shows a plan view of a variation of the inventive stent in whichthe number of torsion members (144) in a selected ring member (146) issignificantly higher then the number of torsion members found in thevariations discussed in relation to FIGS. 7A, 7B, 7C, and 8. This addednumber of torsion members may be due to a variety of reasons. Forinstance, the material of construction may have a significantly lowertolerance for twisting than the materials in those prior Figures. Addingmore torsion bars lessens the load carried on each of the several bars.Alternatively, for the same material, the stent may need be folded to asmaller diameter for deployment than those earlier variations.

FIG. 10 shows a variation of the invention in which the end caps (146)are bound by a long torsion member (148) and two short torsion members(150). This torsion set (152) is in turn separated from the adjacenttorsion set (152) by a bridge member (154) which shores the bending loadof the stent when the stent is rolled and the ends (156) joined by,e.g., welding. The torsion members (150) have a greater width than thatof the long torsion member (148) so to balance the load around the ringduring deformation and thereby to prevent the bridge members frombecoming askew and out of the ring plane.

Although it has been made quite clear that the stents and stent-graftsof this invention do not longitudinally expand as they are deployed, wehave found it desirable in some instances to overlap the rings--a singlecircumference would cross two or more rings--to provide relief fromkinking of the stent-graft. This is also particularly useful at the endsof the stent where additional strength is sometimes needed for securingthe stent in place. Obviously to allow the rings to overlap withoutbuilding thickness, the spacing and size of the end caps and torsionmembers must be tailored to intermesh without contact.

Tubular Component

The tubular component or member of the stent-graft may be made up of anymaterial which is suitable for use as a graft in the chosen body lumen.Many graft materials are known, particularly known are vascular graftmaterials. For instance, natural material may be introduced onto theinner surface of the stent and fastened into place. Synthetic polymerssuch as polyethylene, polypropylene, polyurethane, polyglycolic acid,polyesters, polyamides, their mixtures, blends, copolymers, mixtures,blends and copolymers are suitable; preferred of this class arepolyesters such as polyethylene terephthalate including DACRON and MYLARand polyaramids such as KEVLAR, polyfluorocarbons such aspolytetrafluoroethylene with and without copolymerizedhexafluoropropylene (TEFLON or GORETEX), and porous or nonporouspolyurethanes. Highly preferred materials are certain collagen-basedmaterials of COLLAGEN CORPORATION of Palo Alto, California. The graftmay adhere to or partially encapsulate or be cast about the stent whenappropriate materials such as castable polyurethane or collagen-basedmaterials are employed. When the stent-graft is produced in such a waythat the openings in the stent contain graft material (as by casting),then we refer to such a stent-graft as an "integral stent-graft".

A highly preferred material is a collagen-based material described inU.S. Pat. No. 5,162,430, to Rhee et al, the entirety of which isincorporated by notice, or as described below. Collagen is easily formedinto thin-walled tubes which are limp, compliant, flexible, uniform, andhave smooth surfaces. The tubing walls may have a hydrated thickness of0.001 to 0.020 inches (or to 0.100 inches in some cases) for efficacy.Other thicknesses may be used if specific goals are to be achieved. In astent-graft, the collagen tube acts as an intravascular blood conduit toline the interior surface of the blood vessel. It isolates the linedsegment of the vessel from direct contact with blood flow, tacks anytears or dissections, helps reinforce the vessel wall to protect againstor isolate aneurysms, and provides a smooth, relatively thin, conformalsurface for the blood flow. Of most importance (at least from theperspective of the most preferred aspects of our invention), specificcollagenous materials, such as the collagen-hydrophilic polymerconjugate described in U.S. Pat. No. 5,162,430 and as described below,are very desirable as the tubular component in this stent-graft in thatthey form non-thrombogenic surfaces which will support the growth ofendothelium.

The preferred collagen composition used in this invention is apharmaceutically acceptable non-immunogenic composition formed bycovalently binding atelopeptide collagen to pharmaceutically pure,synthetic, hydrophilic polymers via specific types of chemical bonds toprovide collagen/polymer conjugates. Any type of collagen may be usedincluding extracted and purified collagen including atelopeptidecollagen which can be type I, type II or type III collagen. The collagenmay be extracted from various sources such as bovine hide and humanplacenta and may be fibrillar or non-fibrillar. The synthetichydrophilic polymer may be polyethylene glycol and derivatives thereofhaving a weight average molecular weight over a range of from about 100to about 20,000. The compositions may incorporate other components suchas biologically active materials. The collagen-polymer conjugatesgenerally contain large amounts of water when formed. The extrudedmaterials may be dehydrated, resulting in a reasonably flexible materialwhich can be readily stored.

The term "collagen" as used herein refers to all forms of collagen,including those which have been extracted, processed, or otherwisemodified. Preferred collagens are non-immunogenic and, if extracted fromanimals, are treated to remove the immunogenic telopeptide regions("atelopeptide collagen"), are soluble, and may be in the fibrillar ornon-fibrillar form. Type I collagen is best suited to most applicationsinvolving bone or cartilage repair. However, other forms of collagen arealso useful in the practice of the invention, and are not excluded fromconsideration here. Collagen crosslinked using heat, radiation, orchemical agents such as glutaraldehyde may be conjugated with polymersas described herein to form particularly rigid compositions. Collagencrosslinked using glutaraldehyde or other (nonpolymer) linking agents isreferred to herein as "GAX", while collagen crosslinked using heatand/or radiation is termed "HRX." Collagen used in connection with thepreferred embodiments of the invention is in a pharmaceutically pureform such that it can be incorporated into a body, human or otherwise,for the intended purpose.

The term "synthetic hydrophilic polymer" as used herein refers to asynthetic polymer having an average molecular weight and compositionwhich renders the polymer essentially water-soluble. Preferred polymersare highly pure or are purified to a highly pure state such that thepolymer is, or is treated to become, pharmaceutically pure. Mosthydrophilic polymers can be rendered water-soluble by incorporating asufficient number of oxygen (or, less frequently, nitrogen) atomsavailable for forming hydrogen bonds in aqueous solutions. Preferredpolymers are hydrophilic but not soluble. Preferred hydrophilic polymersused herein include polyethylene glycol, polyoxyethylene, polymethyleneglycol, polytrimethylene glycols, polyvinylpyrrolidones, and derivativesthereof. The polymers can be linear or multiply branched and will not besubstantially crosslinked. Other suitable polymers includepolyoxyethylene-polyoxypropylene block polymers and copolymers.Polyoxyethylene-polyoxypropylene block polymers having an ethylenediamine nucleus (and thus having four ends) are also available and maybe used in the practice of the invention. Naturally occurring and/orbiologically active polymers such as proteins, starch, cellulose,heparin, and the like are not generally desirable in this definitionalthough they may be suitable under some circumstances. All suitablepolymers will be non-toxic, non-inflammatory and non-immunogenic whenused to form the desired composition, and will preferably be essentiallynon-degradable in vivo over a period of at least several months. Thehydrophilic polymer may increase the hydrophilicity of the collagen, butdoes not render it water-soluble. Presently preferred hydrophilicpolymers are mono-, di-, and multi-functional polyethylene glycols(PEG). Monofunctional PEG has only one reactive hydroxy group, whiledifunctional PEG has reactive groups at each end. Monofunctional PEGpreferably has a weight average molecular weight between about 100 andabout 15,000, more preferably between about 200 and about 8,000, andmost preferably about 4,000. Difunctional PEG preferably has a molecularweight of about 400 to about 40,000, more preferably about 3,000 toabout 10,000. Multi-functional PEG preferably has a molecular weightbetween about 3,000 and 100,000.

PEG can be rendered monofunctional by forming an alkylene ether at oneend. The alkylene ether may be any suitable alkoxy radical having 1-6carbon atoms, for example, methoxy, ethoxy, propoxy, 2-propoxy, butoxy,hexyloxy, and the like. Methoxy is presently preferred. Difunctional PEGis provided by allowing a reactive hydroxy group at each end of thelinear molecule. The reactive groups are preferably at the ends of thepolymer, but may be provided along the length thereof.

The term "chemically conjugated" as used herein means attached through acovalent chemical bond. In the practice of the invention, a synthetichydrophilic polymer and collagen may be chemically conjugated by using alinking radical, so that the polymer and collagen are each bound to theradical, but not directly to each other. The term "collagen-polymer"refers to collagen chemically conjugated to a synthetic hydrophilicpolymer, within the meaning of this invention. Thus, "collagen-PEG" (or"PEG-collagen) denotes a composition within the most preferred aspect ofthe invention wherein collagen is chemically conjugated to PEG."Collagen-dPEG" refers to collagen chemically conjugated to difunctionalPEG, wherein the collagen molecules are typically crosslinked."Crosslinked collagen" refers to collagen in which collagen moleculesare linked by covalent bonds with multifunctionally activated (includingdifunctionally activated) polymers. Terms such as "GAX-dPEG" and"HRX-dPEG" indicate collagen crosslinked by both a difunctionallyactivated hydrophilic polymer and a crosslinking agent such asglutaraldehyde or heat. The polymer may be "chemically conjugated" tothe collagen by means of a number of different types of chemicallinkages. For example, the conjugation can be via an ester or urethanelinkage, but is more preferably by means of an ether linkage asdisclosed in PCT publication No. W0940845 to Rhee et al. An etherlinkage is preferred in that it can be formed without the use of toxicchemicals and is not readily susceptible to hydrolysis in vivo.

Those of ordinary skill in the art will appreciate that syntheticpolymers such as polyethylene glycol cannot be prepared practically tohave exact molecular weights, and that the term "molecular weight" asused herein refers to the weight average molecular weight of a number ofmolecules in any given sample, as commonly used in the art. Thus, asample of PEG 2,000 might contain a statistical mixture of polymermolecules ranging in weight from, for example, 1,500 to 2,500 daltonswith one molecule differing slightly from the next over a range.Specification of a range of molecular weight indicates that the averagemolecular weight may be any value between the limits specified, and mayinclude molecules outside those limits. Thus, a molecular weight rangeof about 800 to about 20,000 indicates an average molecular weight of atleast about 800, ranging up to about 20 kDa.

The term "available lysine residue" as used herein refers to lysine sidechains exposed on the outer surface of collagen molecules, which arepositioned in a manner to allow reaction with activated PEG. The numberof available lysine residues may be determined by reaction with sodium2,4,6-trinitrobenzenesulfonate (TNBS).

The term "growth factor" is used to describe biologically activemolecules and active peptides (which may be naturally occurring orsynthetic) which aid in healing or regrowth of normal tissue. Thefunction of growth factors is two-fold: 1) they can incite local cellsto produce new collagen or tissue, or 2) they can attract cells to thesite in need of correction. As such, growth factors may serve toencourage "biological anchoring" of the collagen graft implant withinthe host tissue. As previously described, the growth factors may eitherbe admixed with the collagen-polymer conjugate or chemically coupled tothe conjugate. For example, one may incorporate growth factors such asepidermal growth factor (EGF), transforming growth factor (TGF) alpha,TGF.sub.β (including any combination of TGF.sub.β s), TGF.sub.β1,TGF.sub.β2, platelet derived growth factor (PDGF-AA, PDGF-AB, PDGF-BB),acidic fibroblast growth factor (FGF), basic FGF, connective tissueactivating peptides (CTAP), β-thrombo-globulin, insulin-like growthfactors, erythropoietin (EPO), nerve growth factor (NGF), bonemorphogenic protein (BMP), osteogenic factors, and the like.Incorporation of growth factors can facilitate regrowth when the tubesare used in the treatment of defective or damaged channels. The growthfactors may be attached to free polymer ends by the same method used toattach PEG to collagen, or by any other suitable method. By tetheringgrowth factors to the outer and/or inner surface of the graft material,the amount of grafts needed to carry out effective treatment issubstantially reduced. Tubes which incorporate growth factors mayprovide effective controlled-release drug delivery. By varying thechemical linkage between the collagen and the synthetic polymer, it ispossible to vary the effect with respect to the release of the biologic.For example, when an "ester" linkage is used, the linkage is more easilybroken under physiological conditions, allowing for sustained release ofthe growth factor from the matrix. However, when an "ether" linkage isused, the bonds are not easily broken and the growth factor will remainin place for longer periods of time with its active sites exposedproviding a biological effect on the natural substrate for the activesite of the protein. It is possible to include a mixture of conjugateswith different linkages so as to obtain variations in the effect withrespect to the release of the biologic, e.g., the sustained releaseeffect can be modified to obtain the desired rate of release.

The terms "effective amount" or "amount effective to treat" refer to theamount of composition required in order to obtain the effect desired.Thus, a "tissue growth-promoting amount" of a composition containing agrowth factor refers to the amount of growth factor needed in order tostimulate tissue growth to a detectable degree. Tissue, in this context,includes connective tissue, bone, cartilage, epidermis and dermis,blood, and other tissues with particular emphasis on tissues which formchannels such as veins, arteries, intestines and the like. The actualamount which is determined to be an effective amount will vary dependingon factors such as the size, condition, sex, and age of the patient, thetype of tissue or channel, the effect desired and type of growth factor,and can be more readily determined by the caregiver.

The term "sufficient amount" as used herein is applied to the amount ofcarrier used in combination with the collagen-polymer conjugates used informing the tubes of the invention. A sufficient amount is that amountwhich, when mixed with the conjugate, renders it in the physical formdesired, for example, extrudable tubes, extrudable cylinders having anydesired cross-section, and so forth. Extrudable formulations may includean amount of a carrier sufficient to render the composition smoothlyextrudable without significant need to interrupt the extrusion process.The amount of the carrier can be varied and adjusted depending on thesize and shape and thickness of the wall of the tube being extruded.Such adjustments will be apparent to those skilled in the art uponreading this disclosure.

Conjugates

To form the most desired collagen-conjugates used in the inventivestent-grafts, collagen must be chemically bound to a synthetichydrophilic polymer. This can be carried out in a variety of ways. Inaccordance with the preferred method, the synthetic hydrophilic polymeris activated and then reacted with the collagen. Alternatively, thehydroxyl or amino groups present on the collagen can be activated andthe activated groups will react with the polymer to form the conjugate.In accordance with a less preferred method, a linking group withactivated hydroxyl or amino groups thereon can be combined with thepolymer and collagen in a manner so as to concurrently react with boththe polymer and collagen forming the conjugate. Other methods of formingthe conjugates will become apparent to those skilled in the art uponreading this disclosure. Since the conjugates of the invention are to beused in the human body it is important that all of the components,including the polymer, collagen, and linking group, if used form aconjugate that is unlikely to be rejected by the body. Accordingly,toxic and/or immunoreactive components are not preferred as startingmaterials. Some preferred starting materials and methods of formingconjugates are described further below.

Although different hydrophilic synthetic polymers can be used inconnection with forming the conjugate, such polymers must bebiocompatible, relatively insoluble, but hydrophilic and is preferablyone or more forms of polyethylene glycol (PEG), due to its knownbiocompatibility. Various forms of PEG are extensively used in themodification of biologically active molecules because PEG can beformulated to have a wide range of solubilities and because it lackstoxicity, antigenicity, immunogenicity, and does not typically interferewith the enzymatic activities and/or conformations of peptides. Further,PEG is generally non-biodegradable and is easily excreted from mostliving organisms including humans.

The first step in forming the collagen-polymer conjugates generallyinvolves the functionalization of the PEG molecule. Variousfunctionalized polyethylene glycols have been used effectively in fieldssuch as protein modification (see Abuchowski et al., Enzymes as Drugs,John Wiley & Sons: New York, N.Y. (1981) pp. 367-383; and Dreborg etal., Crit. Rev. Therap. Drug Carrier Syst. (1990) 6:315, both of whichare incorporated herein by reference), peptide chemistry (see Mutter etal., The Peptides, Academic: New York, N.Y. 2:285-332; and Zalipsky etal., Int. J. Peptide Protein Res. (1987) 30:740, both of which areincorporated herein by reference), and the synthesis of polymeric drugs(see Zalipsky et al., Eur. Polym. J. (1983) 19:1177; and Ouchi et al.,J. Macromol. Sci. -Chem. (1987) A24:1011, both of which are incorporatedherein by reference). Various types of conjugates formed by the bindingof polyethylene glycol with specific pharmaceutically active proteinshave been disclosed and found to have useful medical applications inpart due to the stability of such conjugates with respect to proteolyticdigestion, reduced immunogenicity and longer half-lives within livingorganisms.

One form of polyethylene glycol which has been found to be particularlyuseful is monomethoxy-polyethylene glycol (mPEG), which can be activatedby the addition of a compound such as cyanuric chloride, then coupled toa protein (see Abuchowski et al., J. Biol. Chem. (1977) 252:3578, whichis incorporated herein by reference). Although such methods ofactivating polyethylene glycol can be used in connection with thepresent invention, they are not particularly desirable in that thecyanuric chloride is relatively toxic and must be completely removedfrom any resulting product in order to provide a pharmaceuticallyacceptable composition.

Activated forms of PEG can be made from reactants which can be purchasedcommercially. One form of activated PEG which has been found to beparticularly useful in connection with the present invention ismPEG-succinate-N-hydroxysuccinimide ester (SS-PEG) (see Abuchowski etal., Cancer Biochem. Biphys. (1984) 7:175, which is incorporated hereinby reference). Activated forms of PEG such as SS-PEG react with theproteins under relatively mild conditions and produce conjugates withoutdestroying the specific biological activity and specificity of theprotein attached to the PEG. However, when such activated PEGs arereacted with proteins, they react and form linkages by means of esterbonds. Although ester linkages can be used in connection with thepresent invention, they are not particularly preferred in that theyundergo hydrolysis when subjected to physiological conditions overextended periods of time (see Dreborg et al., Crit. Rev. Therap. DrugCarrier Syst. (1990) 6:315; and Ulbrich et al., J. Makromol. Chem.(1986) 187:1131, both of which are incorporated herein by reference).

It is possible to link PEG to proteins via urethane linkages, therebyproviding a more stable attachment which is more resistant to hydrolyticdigestion than the ester linkages (see Zalipsky et al., Polymeric Drugand Drug Delivery Systems, Chapter 10, "Succinimidyl Carbonates ofPolyethylene Glycol" (1991) incorporated herein by reference to disclosethe chemistry involved in linking various forms of PEG to specificbiologically active proteins). The stability of urethane linkages hasbeen demonstrated under physiological conditions (see Veronese et al.,Appl. Biochem. Biotechnol. (1985) 11:141; and Larwood et al., J.Labelled Compounds Radiopharm. (1984) 21:603, both of which areincorporated herein by reference). Another means of attaching the PEG toa protein can be by means of a carbamate linkage (see Beauchamp et al.,Anal. Biochem. (1983) 131:25; and Berger et al., Blood (1988) 71:1641,both of which are incorporated herein by reference). The carbamatelinkage is created by the use of carbonyldiimidazole-activated PEG.Although such linkages have advantages, the reactions are relativelyslow and may take 2 to 3 days to complete.

The various means of activating PEG described above and publications(all of which are incorporated herein by reference) cited in connectionwith the activation means are described in connection with linking thePEG to specific biologically active proteins and not collagen. However,the present invention now discloses that such activated PEG compoundscan be used in connection with the formation of collagen-PEG conjugates.Such conjugates provide a range of improved characteristics and as suchcan be used to form the various compositions used in forming the tubesof the present invention. [Polymeric Drug and Drug Delivery Systems,Chapter 10, "Succinimidyl Carbonates of Polyethylene Glycol" (1991),incorporated herein by reference to disclose the chemistry involved inlinking various forms of PEG to specific biologically active proteins.]

As indicated above, the conjugates used in forming the grafts may beprepared by covalently binding a variety of different types of synthetichydrophilic polymers to collagen. However, because the final product orconjugate obtained must have a number of required characteristics suchas being extrudable from a nozzle, biocompatible and non-immunogenic, ithas been found useful to use polyethylene glycol as the synthetichydrophilic polymer. The polyethylene glycol must be modified in orderto provide activated groups on one or preferably both ends of themolecule so that covalent binding can occur between the PEG and thecollagen. Some specific functionalized forms of PEG are shownstructurally below, as are the products obtained by reacting thesefunctionalized forms of PEG with collagen.

The first functionalized PEG is difunctionalized PEG succinimidylglutarate, referred to herein as (SG-PEG). The structural formula ofthis molecule and the reaction product obtained by reacting it withcollagen is shown in Formula 1. ##STR1##

Another difunctionally activated form of PEG is referred to as PEGsuccinimidyl (S-PEG). The structural formula for this compound and thereaction product obtained by reacting it with collagen is shown inFormula 2. In a general structural formula for the compound of Formula2, the subscript 3 is replaced with an "n." In the embodiment shown inFormula 1, n=3, in that there are three repeating CH₂ groups on eachside of the PEG. The structure in Formula 2 results in a conjugate whichincludes an "ether" linkage which is not subject to hydrolysis. This isdistinct from the first conjugate shown in Formula 1, wherein an esterlinkage is provided. The ester linkage is subject to hydrolysis underphysiological conditions. ##STR2##

Yet another derivatized form of polyethylene glycol, wherein n=2 isshown in Formula 3, as is the conjugate formed by reacting thederivatized PEG with collagen. ##STR3## Another preferred embodiment ofthe invention similar to the compounds of Formula 2 and Formula 3, isprovided when n=1. The structural formula and resulting conjugate areshown in Formula 4. It is noted that the conjugate includes both anether and a peptide linkage. These linkages are stable underphysiological conditions. ##STR4## Yet another derivatized form of PEGis provided when n=0. The difunctionalized form is referred to as PEGsuccinimidyl carbonate (SC-PEG). The structural formula of this compoundand the conjugate formed by reacting SC-PEG with collagen is shown inFormula 5. Although this conjugate includes a urethane linkage, theconjugate has been found not to have a high degree of stability underphysiological conditions. The instability can be a desirablecharacteristic when the tubes are used in a situation where it isdesirable that they dissolve over time. ##STR5##

All of the derivatives depicted in Formulas 1-5 involve the inclusion ofthe succinimidyl group. However, different activating groups can beattached to one or both ends of the PEG. For example, the PEG can bederivatized to form difunctional PEG propionaldehyde (A-PEG), which isshown in Formula 6, as is the conjugate formed by the reaction of A-PEGwith collagen. ##STR6##

Yet another functionalized form of polyethylene glycol is difunctionalPEG glycidyl ether (E-PEG), which is shown in Formula 7, as ##STR7##

The conjugates formed using the functionalized forms of PEG varydepending on the functionalized form of PEG which is used in thereaction. Furthermore, the final product can be varied with respect toits characteristics by changing the molecular weight of the PEG. Ingeneral, the stability of the conjugate is improved by eliminating anyester linkages between the PEG and the collagen and including etherand/or urethane linkages. These stable linkages are generally used toform tubes to replace or repair a blood vessel as may be done with astent-graft. When the grafts are used as a temporary repair unit for adamaged vessel, it may be desirable to include the weaker ester linkagesso that the linkages are gradually broken by hydrolysis underphysiological conditions, breaking apart the tube as it may be replacedby host tissue, or as it degrades, and releasing a component heldtherein, such as a growth factor. By varying the chemical structure ofthe linkage, the rate of sustained release can be varied.

Suitable collagens include all types of pharmaceutically usefulcollagen, preferably types I, II and III. Collagens may be soluble (forexample, commercially available Vitrogen® 100 collagen-in-solution), andmay or may not have the telopeptide regions. Preferably, the collagenwill be reconstituted fibrillar atelopeptide collagen, for exampleZyderm® collagen implant (ZCI) or atelopeptide collagen in solution(CIS). Various forms of collagen are available commercially, or may beprepared by the processes described in, for example, U.S. Pat. Nos.3,949,073; 4,488,911; 4,424,208; 4,582,640; 4,642,117; 4,557,764; and4,689,399, all incorporated herein by reference. Fibrillar,atelopeptide, reconstituted collagen is preferred in order to form tubesused for the repair or replacement of damaged vessels.

Compositions used in forming the invention comprise collagen chemicallyconjugated to a selected synthetic hydrophilic polymer or polymers.Collagen contains a number of available amino and hydroxy groups whichmay be used to bind the synthetic hydrophilic polymer. The polymer maybe bound using a "linking group", as the native hydroxy or amino groupsin collagen and in the polymer frequently require activation before theycan be linked. For example, one may employ compounds such asdicarboxylic anhydrides (e.g., glutaric or succinic anhydride) to form apolymer derivative (e.g., succinate), which may then be activated byesterification with a convenient leaving group, for example,N-hydroxysuccinimide, N,N'-disuccinimidyl oxalate, N,N'-disuccinimidylcarbonate, and the like. See also Davis, U.S. Pat. No. 4,179,337 foradditional linking groups. Presently preferred dicarboxylic anhydridesthat are used to form polymer-glutarate compositions include glutaricanhydride, adipic anhydride, 1,8-naphthalene dicarboxylic anhydride, and1,4,5,8-naphthalenetetracarboxylic dianhydride. The polymer thusactivated is then allowed to react with the collagen, forming acollagen-polymer composition used to make the grafts.

In one highly desirable embodiment having ester linkages, apharmaceutically pure form of monomethylpolyethylene glycol (mPEG) (mw5,000) is reacted with glutaric anhydride (pure form) to create mPEGglutarate. The glutarate derivative is then reacted withN-hydroxysuccinimide to form a succinimidyl monomethylpolyethyleneglycol glutarate. The succinimidyl ester (mPEG*, denoting the activatedPEG intermediate) is then capable of reacting with free amino groupspresent on collagen (lysine residues) to form a collagen-PEG conjugatewherein one end of the PEG molecule is free or nonbound. Other polymersmay be substituted for the monomethyl PEG, as described above.Similarly, the coupling reaction may be carried out using any knownmethod for derivatizing proteins and synthetic polymers. The number ofavailable lysines conjugated may vary from a single residue to 100% ofthe lysines, preferably 10-50%, and more preferably 20-30%. The numberof reactive lysine residues may be determined by standard methods, forexample by reaction with TNBS.

The resulting product is a smooth, pliable, rubbery mass having a shinyappearance. It may be wetted, but is not water-soluble. It may beformulated as a suspension at any convenient concentration, preferablyabout 30-65 mg/mL, and may be extruded through a nozzle to form a tube.The consistency of the formulation may be adjusted by varying the amountof liquid used.

The tubular component may be reinforced using a network of smalldiameter fibers. The fibers may be random, braided, knitted, or woven.The fibers may be imbedded in the tubular component wall, may be placedin a separate layer coaxial with the tubular component, or may be usedin a combination of the two. FIG. 11A shows an end view, cross-sectionof the configuration in which the stent (160) forms the outermost layer,a fibrous layer (162) coaxial to and inside the stent (160), and thetubular component (164) of, e.g., collagen as the inner layer.

Particularly desirable is the variation shown in FIG. 11B in which thefibrous material is mixed with or imbedded into the tubular layer (166)and cast or injected around the stent (160). This fibrous material mayextend the length of the device. Alternatively, randomly oriented shortsegments of fibers may also be imbedded in the wall of the tubing. Thefiber may be DACRON, KEVLAR, or other strong flexible fibers.

In addition, one or more radio-opaque metallic fibers, such as gold,platinum, platinum-tungsten, palladium, platinum-iridium of the like maybe incorporated into the multistrand reinforcement network to allowfluoroscopic visualization of the device.

In the collagen-fiber composite tube, the fibers carry much of the hoopstress and other loadings imposed by the vessel. This relieves theloading on the collagen and significantly increases the burst strengthand fatigue properties of the tube. In addition, this makes the tubemore effective in hydraulically isolating the vessel and as a resultprevents the formation of or worsening of aneurysms. This would beparticularly beneficial in thinned weakened vessel walls resulting fromde-bulking interventions or from medial thinning that has been seen toaccompany stent placement. Another benefit of the fiber reinforcement isthe increase in resistance to radially inward loading, especially if theloading is very focussed. Finally, fiber reinforcement may also impartsome longitudinal stiffness to the stent-graft. This allows thestent-graft to maintain its strength and prevent it from kinking orsagging into the lumen.

Production of the Stent-Graft

The preferred method of constructing the stent-graft is to firstconstruct the stent and then to mold or cast the collagen-based tubularcomponent about the stent.

The stent structure and fiber reinforcement may be molded into the wallof the collagen tube. A mold for such a structure desirably is a simpleannular space between two cylinders having room in the annular spacebetween for placement of the stent and would have a longitudinal axisslightly longer than the length of the stent-graft to be produced. Thestent and fiber tubing is centered in the annular space and then theremaining space filled with collagen. If sPEG cross-linked collagen isused as the matrix material, the sPEG and collagen are mixed andintroduced into the mold and allowed to cure. After curing, the mold isseparated and the inventive fiber reinforced collagen tube with a stentstructure produced.

Deployment of the Invention

When a stent-graft having torsion members is folded, crushed, orotherwise collapsed mechanical energy is stored in torsion in thosetorsion members. In this loaded state the torsion members exert a torqueabout them and consequently have a tendency to untwist. Collectively,the torque exerted by the torsion members are folded down to a reduceddiameter and restrained from springing open. The stent has at least onetorsion member per fold to take advantage of the invention. Thestent-graft is folded along its longitudinal axis and restrained fromspringing open. The stent-graft is then deployed by removing therestraining mechanism, thus allowing the torsion members to spring openagainst the vessel wall.

The attending surgeon will choose a stent or stent-graft having anappropriate diameter. However, inventive devices of this type aretypically selected having an expanded diameter of up to about 10%greater than the diameter of the lumen to be the site of the stentdeployment.

FIG. 12A shows a sequence of folding the device (200) of this inventionabout a guidewire (202) into a loose C-shaped configuration. FIG. 12Bshows a front quarter view of the resulting folded stent or stent-graft.

FIG. 12C shows a sequence of folding the device (200) of this inventionabout a guidewire (202) into a rolled configuration. FIG. 11D shows afront quarter view of the resulting folded stent or stent-graft.

FIG. 12E shows a sequence of folding the device (200) of this inventionabout a guidewire (202) into a triple lobed configuration. FIG. 12Fshows a front quarter view of the resulting folded stent or stent-graft.

The stent-graft may be tracked through the vasculature to the intendeddeployment site and then unfolded against the vessel lumen. Thecollagen-based tube component of the stent-graft is limp, flexible, andthus easy to fold. Folding of the stent structure in the mannerdiscussed above allows it to return to a circular, open configuration.

FIGS. 13A-13C show one desired way to place the devices of the presentinvention and allow them to self-expand. FIG. 13A shows a target site(206) having, e.g., a narrowed vessel lumen. A guidewire (208) having aguide tip (210) has been directed to the site using known techniques.The stent-graft (212) is mounted on guidewire tubing (212) inside outersliding sheath (214) after having folded in the manner discussed above.

FIG. 12B shows placement of the stent-graft (212) at the selected site(206) by sliding the stent-graft (212) over the guidewire (208) alltogether with the guidewire tubing (212) and the outer sliding sheath(214). The stent-graft (212) is deployed by holding the guidewire tubing(212) in a stationary position while withdrawing the outer slidingsheath (214). The stent-graft (212) can be seen in FIG. 13B as partiallydeployed.

FIG. 13C shows the stent-graft (212) fully deployed after the guidewiretubing (212) and the outer sliding sheath (214) have been fullyretracted.

FIGS. 14A-C, 15A-C, and 16A-C show an inventive variation of the stepsof deploying a stent or stent-graft made according to this invention.These methods involve the use of a control line or tether line whichmaintains the stent or stent-graft in a folded configuration untilrelease.

FIG. 14A is a front-quarter view of the stent (302) or stent-graft whichhas been folded as shown in the Figures discussed above. The stent (302)is folded about guidewire (304) so that, when deployed, the guidewire(304) is within the stent (302). Central to the variation shown here isthe tether wire (306) which is passed through loops (308) associatedwith the various rings of the stent (302). The loops (308) may be formedin a variety of ways including simply an alternating weave throughappropriate apexes of the various rings or may be loops specificallyinstalled for the purpose shown here. It should be clear that the tetherwire (306) is so placed that when it is removed by sliding it axiallyalong the stent (302) and out of the loops (308), that the stent (302)unfolds into a generally cylindrical shape within the body lumen.

FIG. 14B shows an end-view of a folded stent (302) or stent-graft havinga guidewire (304) within the inner surface of the stent (302) and withthe tether wire (306) within the loops (308). The end view of the foldedstent (302) shows it to be folded into a form which is generallyC-shaped. When expanded by removal of the tether wire (306), the stent(302) in FIG. 14B assumes the form shown in end view in FIG. 14C. Theremay be seen the guidewire (304) within the lumen of the stent (302) andthe loops (308) which were formerly in a generally linear relationshiphaving a tether wire passing through them.

FIG. 15A shows a folded stent (310) (or stent-graft) in front quarterview which is similar in configuration to the stent (302) shown in FIG.14A except that the stent (310) is rolled somewhat tighter than thepreviously discussed stent. The guidewire (304) is also inside the stent(310) rather than outside of it. Loops (308) from generally opposingsides of the stent (310) are folded into an approximate line so that thetether wire may pass through the aligned loops (308). FIG. 14B shows anend view of the stent (310), and in particular, emphasizes the tighterfold of the stent (310). When expanded by removal of the tether wire(306), the stent (310) in FIG. 15B assumes the form shown in FIG. 14C.In FIG. 15C may be seen the guidewire (304) within the lumen of thestent (310) and the loops (308) which were formerly in a generallylinear relationship having a tether wire passing through them.

FIGS. 16A-C show a schematic procedure for deploying the stent (312) (orstent-graft) using a percutaneous catheter assembly (314).

In FIG. 16A may be seen a percutaneous catheter assembly (314) which hasbeen inserted to a selected site (316) within a body lumen. The stent(312) is folded about the guidewire (319) and guidewire tube (318) heldaxially in place prior to deployment by distal barrier (320) andproximal barrier (322). The distal barrier (320) and proximal barrier(322) typically are affixed to the guidewire tube (318). The tether wire(306) is shown extending through loops (308) proximally through thecatheter assembly's (314) outer jacket (324) through to outside thebody.

FIG. 16B shows the removal of the tether wire (306) from a portion ofthe loops (308) to partially expand the stent (312) onto the selectedsite (316).

FIG. 16C shows the final removal of the tether wire (306) from the loops(308) and the retraction of the catheter assembly (314) from theinterior of the stent (312). The stent (312) is shown as fully expanded.

Many alterations and modifications may be made by those of ordinaryskill in the art without departing from the spirit and scope of theinvention. The illustrated embodiments have been shown only for purposesof clarity and examples, and should not be taken as limiting theinvention as defined by the following claims, which include allequivalents, whether now or later devised.

We claim as our invention:
 1. A method for installing a self-expanding stent into a lumen comprising the steps of:providing a collapsed self-expanding stent having a longitudinal axis and at least one fold line, said stent including at least one assembly extending circumferentially about said longitudinal axis and maintained in said collapsed state by a longitudinally positioned release line associated with said stent, inserting said collapsed self-expanding stent into the lumen, and releasing the collapsed self-expanding stent through an axial directed force applied to said release line to allow the stent to expand at a selected site in a lumen.
 2. The method of claim 1 where the selected site is vascular.
 3. The method of claim 1 in which the collapsed stent is provided by folding the self-expanding stent.
 4. The method of claim 3 in which the folded self-expanding stent is maintained in a collapsed condition prior to release by an exterior sliding sheath.
 5. The method of claim 3 in which the folded self-expanding stent is maintained in a collapsed condition prior to release by a slip line interwoven with said stent.
 6. The method of claim 1 in which the stent comprises a metal.
 7. The method of claim 6 in which the stent comprises a super-elastic alloy.
 8. The method of claim 7 in which the stent comprises a nickel-titanium alloy.
 9. The method of claim 1 in which the at least one assembly comprises a plurality of ring assemblies.
 10. The method of claim 9 where adjacent ring assemblies are joined to one another with longitudinally extending tie members.
 11. The method of claim 1 where said at least one stent assembly has a plurality of serially disposed undulations.
 12. The method of claim 1 where the at least one stent assembly comprises a stainless steel material.
 13. The method of claim 1 where the at least one stent assembly comprises a platinum-tungsten alloy.
 14. The method of claim 1 where the at least one stent ring assembly comprises a sheet material.
 15. The method of claim 1 where the at least one stent ring assembly comprises a wire material.
 16. The method of claim 1 where the at least one stent ring assembly is produced from tubing.
 17. The method of claim 1, wherein said at least one assembly comprises a cobalt chromium alloy.
 18. A method for installing a self-expanding stent-graft into a lumen comprising:providing a collapsed self-expanding stent-graft having a longitudinal axis and at least one fold line, said stent-graft including at least one stent assembly extending circumferentially about said axis and maintained in said collapsed state by a longitudinally positioned release line associated with said stent-graft, and a coaxially positioned tubular graft member, inserting said collapsed self-expanding stent-graft into the lumen, and releasing the collapsed self-expanding stent-graft to allow the stent-graft to expand at the selected site by applying an axially directed force to said release line.
 19. The method of claim 18 where the selected site is vascular.
 20. The method of claim 18 in which the collapsed self-expanding stent-graft is folded.
 21. The method of claim 20 in which the folded self-expanding stent-graft is maintained in a collapsed condition prior to release by an exterior sliding sheath.
 22. The method ot claim 20 in which the folded self-expanding stent-graft is maintained in a collapsed condition prior to release by a slip line interwoven with said stent-graft.
 23. The method of claim 18 in which the stent is metallic.
 24. The method of claim 18 in which the stent is a super-elastic alloy.
 25. The method of claim 18 in which the stent comprises a nickel-titanium alloy.
 26. The method of claim 18 in which the at least one stent assembly comprises a plurality of ring assemblies.
 27. The method of claim 26 wherein adjacent ring assemblies are joined with tie members.
 28. The method of claim 18 where the at least one stent ring assembly has multiple undulations.
 29. The method of claim 18 where the at least one stent ring assembly comprises a sheet material.
 30. The method of claim 18 where the at least one stent ring assembly comprises a wire material.
 31. The method of claim 18 where the at least one stent-graft ring assembly is produced from tubing.
 32. The method of claim 18 wherein the tubular graft member comprises a polyethylene terephthalate.
 33. The method of claim 18 where the tubular member comprises a polyfluorocarbon.
 34. The stent of claim 18 where the tubular craft member comprises a polyurethane.
 35. The method of claim 34 wherein said tubular graft contains radiopaque markers. 